The goals of this proposal are: 1) to develop novel transition metal reduction catalysts for the practical synthesis of chiral alcohols, amines, acids, amino alcohols, diols, alpha and beta-amino acids; 2) to understand the fundamental factors controlling enantioselectivity. This project involves various approaches to ligand design, new protocols for catalytic asymmetric reactions and mechanistic understanding. The P.I. has developed a chiral ligand toolbox for asymmetric hydrogenation of ketones, alkenes, imines and aromatic compounds. A number of excellent ligands systems such as PennPhos, BICP, Ambox, DIOP*, TunePhos, KetalPhos, f-KetalPhos, Binaphane and f-Binaphine have been prepared for Ru, Rh and Ir-catalyzed asymmetric hydrogenation. Recently, the P.l's group has discovered highly active and enantioselective reactions using new electron-donating ligands (TangPhos and Binapine). Many benchmark results have been achieved by the P.I. in area of asymmetric hydrogenation of aliphatic ketones, enamides, unsaturated acids and imines. High activity (up to 50,000 turnovers) and enantioselectivity (up to 99% ee) have been observed for hydrogenation of some substrates. The specific aims of the P.l.'s research involve following transformations: 1) to develop new catalysts for reduction of simple ketones and functionalized ketones, 2) to explore asymmetric hydrogenation of alkenes, 3) to investigate asymmetric hydrogenation of imines and direct reductive amination of ketones, 4) to study asymmetric reduction of aromatic and hetereoaromatic compounds, and 5) to continue the research of developing new chiral ligands. Development of these methods have a direct impact to human health. Practical synthesis of important pharmaceutical compounds are proposed by P. I. Examples include synthesis of lipitor, enalapril, setraline, paxil, dextromorphans and pregabalin.